The role of perturbations in mitochondrial function and in cellular nutrient handling is important in the development and progression of diabetes. Candidate proteins identified that may modulate the nutrient handling and mitochondrial regulatory progrmas in diabetes and nutrient overload have been identified and these are being characterized via functional genomics to evaluate their role in the development of metabolic perturbations and mitochondrial dysfunction in diabetes and obesity. The proteins that are being investigated modulate mitochondrial biology via the modification of lysine residues of mitochondrial proteins the target regulatory proteins modulating these post-translational modifications being explored include acetyl-transferases, deacetylases and ubiquitin ligases. Translational studies are being performed to evaluate whether these experimental findings are valid in the human condition.